This research is conducted jointly by Riverside Research Institute (RRI) and Cornell University Medical College (CUMC). Its long-term objective is to advance the diagnosis, treatment planning, and treatment monitoring of ocular diseases, primarily glaucoma, a leading cause of blindness. Interwoven engineering efforts (at RRI) and clinical studies (at CUMC) will build upon previous methods that have successfully diagnosed ocular tumors by analyzing radio-frequency (RF) echo signals to extract information not available with conventional ultrasound systems. Novel very-high-frequency ultrasound (VHFU) techniques will be used to substantially advance tissue evaluations. Digital RF data will be acquired during multi-plane VHFU scanning of the entire anterior segment. Acquired data will be segmented for use in highly detailed- 3-D representations of anterior structures involved in glaucoma and hypotony. Elements as small as 20 micromoles will be resolved. Biometric data (dimensions, surface areas, volumes) will be derived for relevant compartments, including the anterior chamber and ciliary processes. Internal microstructure of selected volumes will be evaluated in terms of the effective sizes, concentrations, mechanical properties, and shapes of tissue constituents as small as 5 micromoles. Tissue assays will be performed using advanced l-D and 2-D spectral techniques designed using a theoretical scattering model of tissue microstructure. The methods will be validated in laboratory and animal experiments. Measured features will be compared with light and acoustic microscopy to elucidate sensitivity to specific microstructural elements. A statistical framework will relate measurement and system variables to estimator precision. Animal and clinical studies will use data-base techniques to investigate the utility of these methods in evaluating glaucoma, hypotony, and small anterior tumors. Glaucoma studies will assay ciliary body morphology and response to drugs. 3-D techniques will assay the conformation and microstructure of key structures, including ciliary processes, ciliary muscles, and the trabecular meshwork. Studies in normotensive humans will establish control values for tissue parameters as a function of accommodation and age. Chronic open-angle glaucoma patients will be examined to quantify changes in the trabecular meshwork and alterations in ciliary body volume and scattering structure. Effects of glaucoma medication will be quantified. Simplified, standardized output formats of useful parameters will be derived to foster use of these techniques in ophthalmology.